Vascular endothelial growth factor (VEGF) and insulin-like growth factor-I (IGF-I) both play a pivotal role in diabetic microangiopathy. This study assessed the relationship between capillary permeability as a marker of endothelial dysfunction and serum VEGF and IGF-I levels in normotensive diabetics. Subjects were 10 Type 1 (6/4, male/female, age: 30 [mean] +/- 5 [SD] years, HbA1c: 7.5 +/- 1.1 %), 13 Type 2 diabetics (9/4, m/f; 63 +/- 7 years, 8.3 +/- 1.8 %), and 24 age- and sex-matched control subjects. We determined nailfold capillary permeability by intravital fluorescence videomicroscopy after intravenous injection of sodium-fluorescein. Serum VEGF, free and total IGF-I, IGF binding protein (IGFBP)-1, IGFBP-3, and insulin levels were measured by specific immunoassays. Capillary permeability was increased in both types of diabetes patients compared to age- and sex-matched controls. In Type 1 diabetics, fluorescence light intensities increased over time, reaching significance 30 minutes after dye injection. Type 2 diabetics already revealed an early onset of elevated fluorescence light intensities after one minute. Capillary permeability showed a significant positive correlation with VEGF levels in Type 1 diabetics, (r = 0.76, p < 0.05; 20 min after dye injection) but with free IGF-I levels in type 2 diabetics (r = 0.65, p < 0.05; 5 min after dye injection). IGFBP-3 correlated negatively with capillary permeability in both diabetes types, whereas IGFBP-1 levels correlated positively in Type 2 patients. In conclusion, capillary permeability is increased in both types of diabetes mellitus. However, VEGF and IGF-I may differentially affect microvascular permeability depending on the diabetes type.